Pain arising from the viscera is associated with a variety of disorders. The major goal of this research proposal is to improve our understanding of the peripheral mechanisms of visceral pain under normal physiological and pathophysiological conditions. Single fiber studies will be undertaken to understand the role of primary visceral afferents in gastrointestinal (GI) pain. The aims involve characterization of responses of muscle and mucosal afferents in the vagus and splanchnic nerves of the rat to mechanical, thermal and chemical stimuli under normal physiological and inflammatory conditions. Experiments will address the following aims: 1) Quantitative characterization of vagal and splanchnic nerve afferents in these two pathways to graded distension will be compared to understand their relative roles in regulatory functions and nociception. The locations of mechanosensitive receptive fields in the stomach and small intestine will be determined. 2) Determine response-specificity of vagal and splanchnic nerve afferents and determine whether mechanically-insensitive afferents innervating the upper GI tract are truly silent or are chemo- and/or thermo-sensitive. 3) Quantitatively characterize the mechano, thermo- and chemo- sensitive properties of vagal and splanchnic nerve afferents innervating the chronically inflamed stomach and small intestine. 4) Quantitatively characterize the mechano, thermo- and chemo- sensitive properties of vagal and splanchnic nerve afferents innervating the chronically inflamed stomach and small intestine. This proposal represents the first systematic investigation of the possible roles of primary afferents in upper GI pain. The study will provide information about the adequate natural stimuli of the afferents ad about changes in response characteristics during inflammation.